Tacrolimus

Prograf, Astagraf XL, Envarsus XR, Astagraf, Envarsus, Protopic

Immunosuppressant • Calcineurin inhibitor

Premium

NTIQT RiskNephrotoxic

Half-life

11-16 hours

Protein Binding

99%

Metabolized By

CYP3A4, CYP3A5

External

Drugs.com

Boxed warning

Increased susceptibility to infection and malignancy
Post-transplant diabetes mellitus
Use only by physicians experienced in immunosuppression

Clinical alerts

Boxed warning

3 boxed warnings

Narrow therapeutic index

Small dose changes can cause toxicity or loss of effect

QT prolongation

Avoid combining with other QT-prolonging agents; check electrolytes

Nephrotoxic

Monitor renal function; avoid other nephrotoxins where possible

Mechanism of action

Binds to FKBP-12, inhibiting calcineurin and preventing T-cell activation

Recorded indications

From the drug index — may include conditions studied rather than approved indications

·AML
·MDS
·Acute Leukemia
·Acute Myeloid Leukemia
·Myelodysplastic Syndromes

Monitoring

Therapeutic range: 5–15 ng/mL; C0 trough; 10-15 early, 5-10 maintenance

Interactions

2 curated · 2 major or contraindicated · select a row for management

Interacting drug	Severity	Effect
clarithromycin	contraindicated	Severe tacrolimus toxicity with nephrotoxicity and neurotoxicity
fluconazole	major	Tacrolimus toxicity: nephrotoxicity, neurotoxicity, hyperkalemia

Common adverse effects

Nephrotoxicity
Tremor
Headache
Hypertension
Hyperglycemia
Hyperkalemia

Food, alcohol & herbal

Food

Grapefruit increases levels — AVOID
Take consistently with or without food

Alcohol · moderate

May increase tacrolimus levels and toxicity

Herbal

St. John's Wort (major) — Dramatically reduces tacrolimus levels — organ rejection risk

Pharmacokinetics

Published parameters · PMID:15341950

Half-life: 11-16 hours
Protein binding: 99%
Metabolised by: CYP3A4, CYP3A5
Clearance: 25 L/h; adult renal transplant recipients
Volume of distribution: 1300 L
Bioavailability: 25%
Renally eliminated: 2%
Model: 2-compartment

Pregnancy & lactation

Pregnancy category: C
Lactation: avoid

Sources

Assembled from: drug index, curated drug database, curated interaction pairs, published PK literature.

Not a substitute for clinical judgement

Tacrolimus

Prograf, Astagraf XL, Envarsus XR, Astagraf, Envarsus, Protopic

Immunosuppressant • Calcineurin inhibitor

Premium

NTIQT RiskNephrotoxic

Half-life

11-16 hours

Protein Binding

99%

Metabolized By

CYP3A4, CYP3A5

External

Drugs.com

Boxed warning

Increased susceptibility to infection and malignancy
Post-transplant diabetes mellitus
Use only by physicians experienced in immunosuppression

Clinical alerts

Boxed warning

3 boxed warnings

Narrow therapeutic index

Small dose changes can cause toxicity or loss of effect

QT prolongation

Avoid combining with other QT-prolonging agents; check electrolytes

Nephrotoxic

Monitor renal function; avoid other nephrotoxins where possible

Mechanism of action

Binds to FKBP-12, inhibiting calcineurin and preventing T-cell activation

Recorded indications

From the drug index — may include conditions studied rather than approved indications

·AML
·MDS
·Acute Leukemia
·Acute Myeloid Leukemia
·Myelodysplastic Syndromes

Monitoring

Therapeutic range: 5–15 ng/mL; C0 trough; 10-15 early, 5-10 maintenance

Interactions

2 curated · 2 major or contraindicated · select a row for management

Interacting drug	Severity	Effect
clarithromycin	contraindicated	Severe tacrolimus toxicity with nephrotoxicity and neurotoxicity
fluconazole	major	Tacrolimus toxicity: nephrotoxicity, neurotoxicity, hyperkalemia

Common adverse effects

Nephrotoxicity
Tremor
Headache
Hypertension
Hyperglycemia
Hyperkalemia

Food, alcohol & herbal

Food

Grapefruit increases levels — AVOID
Take consistently with or without food

Alcohol · moderate

May increase tacrolimus levels and toxicity

Herbal

St. John's Wort (major) — Dramatically reduces tacrolimus levels — organ rejection risk

Pharmacokinetics

Published parameters · PMID:15341950

Half-life: 11-16 hours
Protein binding: 99%
Metabolised by: CYP3A4, CYP3A5
Clearance: 25 L/h; adult renal transplant recipients
Volume of distribution: 1300 L
Bioavailability: 25%
Renally eliminated: 2%
Model: 2-compartment

Pregnancy & lactation

Pregnancy category: C
Lactation: avoid

Sources

Assembled from: drug index, curated drug database, curated interaction pairs, published PK literature.

Not a substitute for clinical judgement

Tacrolimus Drug Profile | PharmaGraphX